Emerging contrast agents for photoacoustic imaging.

This issue of Contrast Media and Molecular Imaging (CMMI) is dedicated to the topic of photoacoustic or optoacoustic imaging. Photoacoustic tomography (PAT) utilizes a short-pulsed laser light to induce thermo-elastic expansion of proteins (such as hemoglobin) and contrast agents, which then produce pressure waves (photoacoustic waves) that are received on a wide-band ultrasonic transducer and converted to images. Our lead paper from the laboratory of Dr Lihong Wang illustrates how the strong optical scattering of tissue that initially restricted PAT to superficial in vivo imaging has been overcome to permit multi-scale imaging at depths from sub-millimeter to several centimeters with spatial resolutions from sub-micrometer to sub-millimeter. Clearly, PAT is an emergent technology that will enable anatomical, functional, molecular and fluid-dynamic imaging at various biological system levels. Complementing the inherent strengths of PAT is the ongoing development of new contrast agents and new hybrid technologies. Dr Zharov, a recognized leader in this field, shares his broad experience in molecular photoacoustic (PA) imaging, cytometry, and nanotheranostics using photothermal (PT)-based effects for integrated diagnosis and therapy with nanoparticles (NPs). While the Zharov lab report emphasizes carbon nanotube-based contrast agents, his team and collaborators describe the differential challenges for imaging static vs dynamic targets. They present new and related concepts such as nanophotothermolysis of tumor cells and bacteria, PT/PAmultispectral histology, monitoring of NPs in plants, in vivomulticolor blood and lymph flow cytometry, and NP-microbubble conjugates for nanothrombolysis. Gold nanorods offer unique opportunities for optical imaging. Dr Srirang et al. discuss the role of gold nanorods in molecular imaging with photoacoustics and examine the implications of chemical, physical and biochemical phenomena on future photoacoustic applications. Bedrock issues such as minimizing toxicity, functionalizing surfaces and manipulating particle biodistribution are presented to orient interested researchers to the synthetic approaches used to overcome in vivo barriers to clinical translation. Dr Xia describes the unique chemistry and opportunities posed by gold nanocages, which are characterized by their hollow interiors and ultrathin porous walls. Their compact size, bioinertness and well-defined surface chemistry, combined with a strong and highly wavelength-tunable optical absorption in the near-infrared window of soft tissues, make them particularly attractive as exogenous contrast agent. In another paper, Drs Pan and Lanza summarize their efforts to advance molecular PAT imaging with colloidal gold nanobeacons. Gold nanobeacons are a robust nanoparticle platform that entraps multiple copies of tiny spherical gold nanoparticles (2–4nm) within a larger colloidal particle encapsulated by biocompatible synthetic or natural amphilines. The utilization of numerous small gold particles greatly amplifies the signal without exceeding the 6nm renal elimination threshold size of humans, while the large particle dimension is optimal for vascular imaging, such as specific delineation of angiogenesis from small but maturing microvessels. Finally, Dr Xu et al. introduce PAT contrast opportunities associated with theranostic multifunctional microand nanobubbles. Their work, although still early, describes an approach based on encapsulation of highly absorbing optical contrast agents, such as gold nanoparticles, India ink and indocyanine green, for development of multimodal imaging contrasts. The advantages of surface functionalization of the bubbles for high affinity for disease-targeting, reduced immunogenicity and prolonged circulation lifetime are shared. Moreover, the combined use of low-boiling-point perfluorocarbon compounds, activatable by external energy sources, is proffered as a personalized approach to image-guided drug delivery. Although photoacoustic imaging is a nascent technology, it has received broad interest for clinical translation by major manufacturers of biomedical imaging instrumentation. Within the last year, VisualSonics Inc. and Endra Inc. have already brought animal research scanners to the market to support contrast development. For the reader, this special issue provides a definitive presentation of the photoacoustic imaging and related contrast agents, which we hope will enthuse experimentation to advance and refine these technologies for basic and clinical applications.